This invention relates to pyridines substituted at the 4-position with a thioether and carboxy, (C.sub.2 -C.sub.5)carboalkoxy or formyl containing side chain, and the pharmaceutically acceptable salts thereof, having utility in the treatment of arthritis as well as utility as intermediates for the preparation of the corresponding alcohols having the same utility.
A number of compounds have been known in the art to possess immunoregulatory activity, and thus have been proposed for use in the treatment of rheumatoid arthritis and related conditions where regulation of the immune response is desired. For example, such conditions have been treated by administration of an immunoregulatory agent such as levamisole, as described in Arthritis and Rheumatism, 20, 1445 (1977) and Lancet, 1, 393 (1976). In efforts to find new and improved therapeutic agents for the treatment of these conditions, it has now been found that the pyridines of the present invention are active as regulants of the immune response in mammals, and are thus of particular value in the treatment of rheumatoid arthritis and other conditions where regulation of the immune response is desired.
Not all of the compounds of the present invention are novel. Thus, acids and esters of the formula (I) wherein n=1 and Z=hydroxy or (C.sub.1 -C.sub.4)alkoxy have been disclosed as compounds useful as intermediates in the preparation of cephalosporin derivatives, British Patent Specification No. 1,434,271 (1976); specifically described are 2-(4-picolylthio)acetic acid and methyl 2-(4-picolylthio)acetate. Isomeric 2-(2-carboxyethylthiomethyl)pyridine has also been reported (in Example 30 of British Patent Specification No. 1,213,049); the latter compound is claimed to be useful for treating inflammation in non-human animals, but is not disclosed as having the desirable immunoregulatory activity of the present compounds. In this regard, it is noteworthy that the derived alcohol of that British patent (Example 31) is devoid of the present immunoregulatory activity at a level where alcohols derived from the present compounds have a high level of such activity.